The objective of the proposed research is to characterize prolactin-receptor regulation in normal rat mammary tissue and in hormone-dependent rat mammary carcinoma. Using primary cultures of prolactin-stimulated normal mammary gland and DMBA-induced, rat mammary tumors which retain prolactin receptors and prolactin responsiveness, we will investigate (1) the direct effects of insulin, progesterone, androgen and estrogen on the level of prolactin-receptor sites, (2) the autoregulation of prolactin receptors, (3) the cellular location of prolactin and prolactin receptor sites from autoradiographic and immunocytochemical studies, and (4) any cell-cycle-specific changes in prolactin receptors. We will determine if the activities of guanyl cyclase and ornithine decarboxylase and the uptake of alpha aminoisobutyric acid are influenced by prolactin and correlated with the number of prolactin receptors and cell growth. The results of these studies should provide a more complete understanding of the mechanism by which prolactin controls the growth of normal and hormone-dependent neoplastic mammary tissue.